VIRAL GENETIC-VARIATION, AIDS, AND THE MULTISTEP NATURE OF CARCINOGENESIS - THE FELINE LEUKEMIA-VIRUS MODEL

Feline leukemia virus (FeLV) infection in cats serves as a valuable an imal model system for understanding the mechanisms of human diseases s uch as cancer and immunodeficiency. We have used experimental infectio n with molecularly cloned viruses to isolate and characterize novel Fe LV variants that evolved in vivo and that were associated with the dev elopment of thymic lymphoma. One variant, FeLV-81T, contained a mutate d envelope gene that conferred cytopathicity, enhanced replication rat e, and syncytium induction in feline T cells, and is reminiscent of im munodeficiency-inducing strains of FeLV. Another variant transduced a portion of the feline Notch2 gene, which was expressed as a novel trun cated protein in the cell nucleus and which we believe functioned as a n oncogene in the development of T cell malignancy. Understanding how FeLV variants that either stimulate or destroy lymphocytes evolve and interrelate during disease progression will help elucidate the mechani sms of retroviral pathogenicity.